Hematopoietic cell transplantation donor-derived memory-like NK cells functionally persist after transfer into patients with leukemia.

Autor:	Berrien-Elliott MM; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Foltz JA; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Russler-Germain DA; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Neal CC; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Tran J; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Gang M; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Wong P; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Fisk B; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Cubitt CC; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Marin ND; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Zhou AY; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Jacobs MT; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Foster M; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Schappe T; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., McClain E; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Kersting-Schadek S; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Desai S; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Pence P; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Becker-Hapak M; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Eisele J; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Mosior M; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Marsala L; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Griffith OL; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA., Griffith M; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA., Khan SM; Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA., Spencer DH; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., DiPersio JF; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Romee R; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Uy GL; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Abboud CN; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Ghobadi A; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Westervelt P; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Stockerl-Goldstein K; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Schroeder MA; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Wan F; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA., Lie WR; MilliporeSigma, St. Louis, MO 68178, USA., Soon-Shiong P; ImmunityBio Inc., Culver City, CA 90245, USA., Petti AA; Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA., Cashen AF; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Fehniger TA; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
Jazyk:	angličtina
Zdroj:	Science translational medicine [Sci Transl Med] 2022 Feb 23; Vol. 14 (633), pp. eabm1375. Date of Electronic Publication: 2022 Feb 23.
DOI:	10.1126/scitranslmed.abm1375
Abstrakt:	Natural killer (NK) cells are innate lymphoid cells that eliminate cancer cells, produce cytokines, and are being investigated as a nascent cellular immunotherapy. Impaired NK cell function, expansion, and persistence remain key challenges for optimal clinical translation. One promising strategy to overcome these challenges is cytokine-induced memory-like (ML) differentiation, whereby NK cells acquire enhanced antitumor function after stimulation with interleukin-12 (IL-12), IL-15, and IL-18. Here, reduced-intensity conditioning (RIC) for HLA -haploidentical hematopoietic cell transplantation (HCT) was augmented with same-donor ML NK cells on day +7 and 3 weeks of N-803 (IL-15 superagonist) to treat patients with relapsed/refractory acute myeloid leukemia (AML) in a clinical trial (NCT02782546). In 15 patients, donor ML NK cells were well tolerated, and 87% of patients achieved a composite complete response at day +28, which corresponded with clearing high-risk mutations, including TP53 variants. NK cells were the major blood lymphocytes for 2 months after HCT with 1104-fold expansion (over 1 to 2 weeks). Phenotypic and transcriptional analyses identified donor ML NK cells as distinct from conventional NK cells and showed that ML NK cells persisted for over 2 months. ML NK cells expressed CD16, CD57, and high granzyme B and perforin, along with a unique transcription factor profile. ML NK cells differentiated in patients had enhanced ex vivo function compared to conventional NK cells from both patients and healthy donors. Overall, same-donor ML NK cell therapy with 3 weeks of N-803 support safely augmented RIC haplo-HCT for AML.
Databáze:	MEDLINE
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